Secondary and tertiary structure are important to the function of many naturally occurring RNA. In this proposal we described several approaches to the investigation of RNA structure in solution including high resolution NMR (NOE, relaxation, saturation transfer), photochemical mapping of secondary structure and other spectroscopic methods (ESR, hypochromisim, fluorescence quenching). Four areas of research are proposed: 1. structural studies of tRNA, 2. secondary structure in 5S RNA, messenger RNA and other RNA, 3. structural properties of simple sequence RNA helices, and 4. molecular mechanisms of RNA recognition by small molecules. In the tRNA studies we are concerned with location of and factors responsible for the strong metal ion binding sites on tRNA, environmental effects on tRNA structure, functional role of non Watson Crick base pairs, quantitative comparison of the crystal and solution state structures, and nature of tRNA-drug interactions. With the larger RNA, NMR will be used along with a new photochemical method to map secondary structure. Simple sequence RNA helices will be studied to determine hydrogen bonding schemes for non Watson Crick pairing, tautomeric states, stoichiometery, and ultimately precise helical conformations. Finally, the well characterized tRNA and RNA helices will be used to study fundamental interactions involved in the recognition of RNA by various ions and molecules. These studies are significant because (1) the molecules chosen for study are biologically important, (2) their functions are affected by their secondary and tertiary structure, and (3) novel methods are proposed to investigate the secondary and tertiary structure of RNA in solution.